Registration Number
0223U001038,
0121U109941
, R & D reports
Title
Photocontrolled analogues of natural cytotoxic peptides for immunotherapy of metastatic cancer
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Head
Komarov Ihor V., Доктор хімічних наук
Registration Date
24-01-2023
Organization
Taras Shevchenko National University of Kyiv
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Research object: Peptides with photo-controlled cytotoxic properties.
The purpose of the work: design, synthesis, research of peptides that, upon photoactivation in tumors, cause immunogenic cell death and, as а result, а powerful reaction of the immune system, which can Ье used in innovative approaches to cancer
immunotherapy.
Research methods: organic synthesis, computer modeling, analysis using physical methods, confocal fluorescence microscopy.
Natural cytotoxic peptide Gymnopeptide В, as well as its photocontrolled analogs with different positions of the diarylethene photosensitive fragment in the molecules, were comprehensively investigated Ьу molecular dynamics methods.
According to the results of the calculations, such analogues were found, which have significantly different molecular structures depending on the photoisomeric form of the diarylethene fragment. Among these analogs, the one that has one of the photoisomeric forms most similar in structure and dynamics to the prototype, Gymnopeptide В, was selected for further synthesis. Gymnopeptide В and two of its photosensitive analogs were synthesized. The newly synthesized peptides showed а significant cytotoxic effect against the HeLa cancer cell line - at the level of the well-known anticancer drug - Cisplatin. However, photoregulation of the biological action of these peptides proved to bе insufficient for their practical use in cancer photopharmacology. Cytotoxicity and effectiveness of antitumor action, signs of immune system activation were studied using model compounds whose photocontrol is sufficiently effective, peptides LMB002, LМВОЗЗ and LMB040 (analogs of Gymnopeptide В), in vitro and on а
chemically induced model of hepatocellular carcinoma in rats. Also, photoactivation of peptides in model tissues using high-performance liquid chromatography was investigated on model compounds.
Product Description
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Garmanhuk Ludmila V.
Danko Volodymyr P.
Kovalenko Andriy V.
Radchenko Dmytro S.
Tsuvariev Oleksandr Yu.
Yanchuk Petro І.
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2023-01-24
